Producing Alzheimer's Symptoms in Rats via a Transplanted Gut Microbiome

The gut microbiome changes with age, the relative population sizes of the many distinct microbial species altering to provoke chronic inflammation and potentially other, more complex issues driven by changes in the production of beneficial and harmful metabolites. With the advent of ways to cheaply assess the contents of the gut microbiome, researchers are finding that a number of age-related conditions appear characterized by dysbiosis, growth in the population of specific harmful microbial species. One of those conditions is Alzheimer's disease, which has a puzzling incidence that doesn't track well with the well established lifestyle risk factors for inflammatory disease. If it is instead primarily driven by specific alterations to the gut microbiome, that might go some way towards explaining why only some people progress from mild cognitive impairment to Alzheimer's disease.

The study reported in today's research materials is intended to extend existing correlational data in humans to demonstrate whether or not an Alzheimer's-like gut microbiome can produce pathology when introduced into animal models, rats in this case. As such, the usual caveats to apply, in that rodents do not normally develop anything resembling Alzheimer's disease. Nonetheless, it is intriguing to see that Alzheimer's patient microbiomes cause cognitive issues in rats when compared to the effects of a non-Alzheimer's aged human microbiome. The observed effects are likely a matter of a greater induction of chronic inflammation in the rats by the Alzheimer's microbiome, but it is plausible that other microbiome-related mechanisms operate in humans to contribute to the risk of Alzheimer's disease, but not in rats because rats cannot naturally develop Alzheimer's disease. If it were only a matter of risk scaling with chronic inflammation, then being overweight or obese would have a far greater correlation with Alzheimer's disease risk than is actually the case.

Scientists discover links between Alzheimer's disease and gut microbiota

For the first time, researchers have found that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming its role in the disease. The study shows that that the memory impairments in people with Alzheimer's could be transferred to young rats through transplant of gut microbiota. The study supports the emergence of the gut microbiome as a key target for investigation in Alzheimer's disease due to its particular susceptibility to lifestyle and environmental influences. Alzheimer's patients had a higher abundance of inflammation-promoting bacteria in faecal samples, and these changes were directly associated with their cognitive status.

Microbiota from Alzheimer's patients induce deficits in cognition and hippocampal neurogenesis

To understand the involvement of Alzheimer's patient gut microbiota in host physiology and behaviour, we transplanted faecal microbiota from Alzheimer's patients and age-matched healthy controls into microbiota-depleted young adult rats. We found impairments in behaviours reliant on adult hippocampal neurogenesis, an essential process for certain memory functions and mood, resulting from Alzheimer's patient transplants. Notably, the severity of impairments correlated with clinical cognitive scores in donor patients. Discrete changes in the rat caecal and hippocampal metabolome were also evident. As hippocampal neurogenesis cannot be measured in living humans but is modulated by the circulatory systemic environment, we assessed the impact of the Alzheimer's systemic environment on proxy neurogenesis readouts. Serum from Alzheimer's patients decreased neurogenesis in human cells in vitro and were associated with cognitive scores and key microbial genera.

Our findings reveal for the first time, that Alzheimer's symptoms can be transferred to a healthy young organism via the gut microbiota, confirming a causal role of gut microbiota in Alzheimer's disease, and highlight hippocampal neurogenesis as a converging central cellular process regulating systemic circulatory and gut-mediated factors in Alzheimer's.